The symptomatic hemoglobinopathies remain significant clinical conditions for which successful treatment has not yet been found. During recent years fundamental research has been focused primarily at the genetic control of hemoglobin synthesis and at post-transcriptional chemical modification of hemoglobin. The proposed research will study single carbon modification of hemoglobin molecules by means of enzymatic and non-enzymatic methylation. The former is mediated by a protein methylase system in erythroid cells and the latter by such agents as formaldehyde and methyl iodide. The nature and sites of the methyl-hemoglobin bonds will be investigated, along with the functional properties of the modified hemoglobin. The effects of methylation on hemoglobin sickling will be studied. Methylating agents also cause cross-linking into higher molecular weight "heavy hemoglobins." The chemistry of this aggregation, as well as its effects on sickling and other functional properties of hemoglobin, will also be investigated. BIBLIOGRAPHIC REFERENCES: Gabuzda, T.G.: Sickle Cell Leg Ulcers: Current Pathophysiologic Concepts. International J. Dermatology, Vol. 14, June 1975, p. 322-325. Holroyde, C.P., Putnam, R.C., Gabuzda, T.G., Reichard, G.A.: Glucose Metabolism in Cancer Patients with and without Progressive Weight Loss. Clin. Research, 23, 322A, 1975.